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Exploratory analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients receiving neo-adjuvant chemotherapy for operable breast cancer.

ABSTRACT: BACKGROUND:While combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun testing in patients with breast cancer (BC), the effects of chemotherapy on ICP expression in circulating T cells and within the tumor microenvironment are still unclear. This information could help with the design of future clinical trials by permitting the selection of the most appropriate ICP inhibitors for incorporation into NAC. METHODS:Peripheral blood samples and/or tumor specimens before and after NAC were obtained from 24 women with operable BC. The expression of CTLA4, PD-1, Lag3, OX40, and Tim3 on circulating T lymphocytes before and at the end of NAC were measured using flow cytometry. Furthermore, using multi-color immunohistochemistry (IHC), the expression of immune checkpoint molecules by stromal tumor-infiltrating lymphocytes (TILs), CD8+ T cells, and tumor cells was determined before and after NAC. Differences in the percentage of CD4+ and CD8+ T cells expressing various checkpoint receptors were determined by a paired Student's t-test. RESULTS:This analysis showed decreased ICP expression by circulating CD4+ T cells after NAC, including significant decreases in CTLA4, Lag3, OX40, and PD-1 (all p values

SUBMITTER: Wesolowski R

PROVIDER: S-EPMC7236344 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Exploratory analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients receiving neo-adjuvant chemotherapy for operable breast cancer.

Wesolowski Robert R Stiff Andrew A Quiroga Dionisia D McQuinn Christopher C Li Zaibo Z Nitta Hiroaki H Savardekar Himanshu H Benner Brooke B Ramaswamy Bhuvaneswari B Lustberg Maryam M Layman Rachel M RM Macrae Erin E Kassem Mahmoud M Williams Nicole N Sardesai Sagar S VanDeusen Jeffrey J Stover Daniel D Cherian Mathew M Mace Thomas A TA Yu Lianbo L Duggan Megan M Carson William E WE

BMC cancer 20200519 1

<h4>Background</h4>While combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun testing in patients with breast cancer (BC), the effects of chemotherapy on ICP expression in circulating T cells and within the tumor microenvironment are still unclear. This information could help with the design of future clinical trials by permitting the selection of the most appropriate ICP inhibitors for incorporation into NAC.<h4>Methods</h4>Peripheral blood samples a ...[more]

PMID: 32429929

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Project description:BackgroundPopulation-based studies suggest that emergency department visits and hospitalizations are common among patients receiving chemotherapy and that rates in routine practice are higher than expected from clinical trials. Chemotherapy-related toxicities are often predictable and, consequently, acute care visits may be preventable with adequate treatment planning and support between visits to the cancer centre. We will evaluate the impact of proactive telephone-based toxicity management on emergency department visits and hospitalizations in women with early stage breast cancer receiving chemotherapy.MethodsIn this pragmatic covariate constraint-based cluster randomized trial, 20 centres in Ontario, Canada are randomly allocated to either proactive telephone toxicity management (intervention) or routine care (control). The primary outcome is the cluster-level mean number of ED + H visits per patient evaluated using Ontario administrative healthcare data. Participants are all patients with early stage (I-III) breast cancer commencing adjuvant or neo-adjuvant chemotherapy at participating institutions during the intervention period. At least 25 patients at each centre participate in a patient reported outcomes sub-study involving the collection of standardized questionnaires to measure: severity of treatment toxicities, self-care, self-efficacy, quality of life, and coordination of care. Patients participating in the patient reported outcomes (PRO) sub-study are asked to provide written consent to link their PRO data to administrative data. Unit costs will be applied to each per person resource utilized, and a total cost per population and patient will be generated. An incremental cost-effectiveness analysis will be undertaken to compare the incremental costs and outcomes between the intervention and control groups from the health system perspective.DiscussionThis study evaluates the effectiveness of a proactive toxicity management intervention in a routine care setting. The use of administrative healthcare data to evaluate the primary outcome enables an evaluation in a real world setting and at a much larger scale than previous studies.Trial registrationClinicaltrials.gov , NCT02485678. Registered 30 June 2015.

Project description:IntroductionThe essential goal of neoadjuvant chemotherapy (NACT) is to downstage the primary tumor making it amenable for breast conservation surgery (BCS). However, since the safety of this surgery is paramount, post-NACT breast conservation rates remain low. As per the recommendation of the 2018 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of long-term post-NACT follow-up, we have devised a protocol for imaging, localization, rad-path analysis, and documentation of radiotherapy techniques to ensure the safety of post-NACT breast conservation.MethodsThis is a retrospective cohort of 180 breast cancer patients who received NACT and were operated on by a single surgical oncologist from 2015 to 2020. After selection based on published guidelines, patients were treated with neoadjuvant systemic (chemo or hormone) therapy. In cases where primary tumors responded and reduced to 1-2 cm in size mid-NACT, the residual tumors were localized by clips under ultrasound guidance and calcification was wire localized. All patients were treated using appropriate surgical and oncoplastic techniques where indicated. Negative margins were ensured by intra-operative rad-path analysis. Adjuvant chemotherapy and radiotherapy were given as per protocol.ResultsIn 81 cases that required mastectomy at presentation, we were able to achieve a 72.8% post-NACT BCS rate with the help of oncoplasty. Overall, 142 of 180 (80%) patients were treated with breast conserving surgery of which 80% (121 of 142) were oncoplasty. Margins were assessed on intra-operative frozen and re-excised in the same setting. No positive margins were reported in final histopath of 142 breast conservation procedures. Post-operative complication rates after breast conservation in the first year were at 17% (24 of 142 including two major complications). Patient reported outcomes were satisfactory with increased satisfaction for breast conservation compared with immediate breast reconstruction.DiscussionEmploying oncoplastic breast surgery (OBS) techniques following stringent protocols for accurate localization of the residual tumor, intra-operative rad-path analysis, and adjuvant treatments, we show successful breast conservation in 72.8% of our mastectomy-qualified patients after downstaging by NACT. We also report satisfactory outcomes for post-NACT surgery, patient-reported satisfaction, and survival.

Dataset Information

Exploratory analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients receiving neo-adjuvant chemotherapy for operable breast cancer.

Publications

Exploratory analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients receiving neo-adjuvant chemotherapy for operable breast cancer.

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